Sputum Culture Conversion In Patients Research Articles

Time to sputum culture conversion and its associated factors among drug-resistant tuberculosis patients: a systematic review and meta-analysis

ObjectiveWe aimed to evaluate the sputum culture conversion time of DR-TB patients and its related factors.MethodsPubMed, The Cochrane Library, Embase, CINAHL, Web of Science, CNKI, Wan Fang, CBM and VIP databases were electronically searched to collect studies on sputum culture conversion time in patients with DR-TB. Meta-analysis was performed by using the R 4.3.0 version and Stata 16 software.ResultsA total of 45 studies involving 17373 patients were included. Meta-analysis results showed that the pooled median time to sputum culture conversion was 68.57 days (IQR 61.01,76.12). The median time of sputum culture conversion in patients with drug-resistant tuberculosis was different in different WHO regions, countries with different levels of development and different treatment schemes. And female (aHR = 0.59,95%CI: s0.46,0.76), alcohol history (aHR = 0.70,95%CI:0.50,0.98), smoking history (aHR = 0.58,95%CI:0.38,0.88), history of SLD use (aHR = 0.64,95%CI:0.47,0.87), BMI < 18.5 kg/m2 (aHR = 0.69,95%CI:0.60,0.80), lung cavity (aHR = 0.70,95%CI:0.52,0.94), sputum smear grading at baseline (Positive) (aHR = 0.56,95%CI:0.36,0.87), (grade 1+) (aHR = 0.87,95%CI:0.77,0.99), (grade 2+) (aHR = 0.81,95%CI:0.69,0.95), (grade 3+) (aHR = 0.71,95%CI:0.61,0.84) were the related factor of sputum culture conversion time in patients with DR-TB.ConclusionPatients with DR-TB in Europe or countries with high level of economic development have earlier sputum culture conversion, and the application of bedaquiline can make patients have shorter sputum culture conversion time. Female, alcohol history, smoking history, history of SLD use, BMI < 18.5 kg/m2, lung cavity, sputum smear grading at baseline (Positive, grade 1+, grade 2+, grade 3+) may be risk factors for longer sputum culture conversion time.This systematic review has been registered in PROSPERO, the registration number is CRD42023438746.

Ceftriaxone efficacy for Mycobacterium avium complex lung disease in the hollow fiber and translation to sustained sputum culture conversion in patients.

Only 35.6%-50.8% of patients with Mycobacterium avium complex (MAC) pulmonary disease achieve sustained sputum culture conversion (SSCC) on treatment with the azithromycin-ethambutol-rifabutin standard of care (SOC). We tested the efficacy of ceftriaxone, a β-lactam with a lung penetration ratio of 12.18-fold. We mimicked lung concentration-time profiles of seven ceftriaxone once-daily doses for 28 days in the hollow fiber system model of intracellular MAC (HFS- MAC). Monte Carlo experiments were used for dose selection.We also compared the once-daily ceftriaxone monotherapy to three-drug SOC against five MAC clinical isolates in HFS-MAC using γ (kill)-slopes. Results were translated to SSCC rates. Ceftriaxone killed 1.02-3.82 log10 cfu/mL in dose-response studies. Ceftriaxone 2G once-daily was identified as the optimal dose. Ceftriaxone killed all five strains below day 0 versus 2/5 for SOC. The median γ (95% confidence interval) was 0.49(0.47-0.52) log10 cfu/mL/day for ceftriaxone and 0.38(0.34-0.43) log10 cfu/mL/day for SOC. In patients, the SOC was predicted to achieve SSCC rates of 39.3%(36%-42%) at 6 months (similar to meta-analyses results). The SOC SSCC was 50% at 8.18(3.64-27.66) months versus 3.58(2.20-7.23) months for ceftriaxone. Thus, ceftriaxone shortened time-to-SSCC 2.35-fold compared to SOC. Ceftriaxone is a promising agent for creation of short-course chemotherapy.

Factors Associated with Acid Fast Bacilli and Sputum Culture Conversion in Patients with Multidrug-Resistant Tuberculosis in Surabaya

Introduction: Indonesia is a high incidence country of multidrug-resistant tuberculosis. There are approximately 11,000 MDR TB cases, 2.8% of them are new cases and 16% of them are relapse cases. Although guidelines for MDR-TB are frequently designed, medication freely provided, and centers for treatment duly expanded, studies on time to sputum culture conversion have been very limited in Indonesia. Therefore the aim of the study is to identify risk factors that effect on sputum and culture conversion.Methods: Data on short-term regimen for MDR TB in Dr. Soetomo General Hospital from January 1st – December 31st, 2018 were collected with a total sampling approach, and fulfill the inclusion and exclusion. Data were analyzed by computer software IBM SPSS Statistic 24 for windows. Results: Male is more likely to have delayed sputum conversion and culture conversion but no statistical difference is observed (p&gt;0.05). Smoking history is more likely to have delayed sputum and culture conversion but only in sputum smear test shows a significant difference (p≤ 0.05). Alcohol consumption has delay effect on sputum and culture conversion but there is statistically difference in only culture conversion (p&lt;0.05). The high baseline smear test also affects delay the sputum and culture conversion but only in sputum smear reveals a significant effect (p&lt;0.05).Conclusion: In this present study, we identified sex, smoking history, high bacillary loads as significant factors on sputum conversion. In addition, we revealed that alcohol-consumption history is a significant factor affecting on culture conversion.

Genotypic Resistance of Pyrazinamide but Not Minimum Inhibitory Concentration Is Associated With Longer Time to Sputum Culture Conversion in Patients With Multidrug-resistant Tuberculosis.

Pyrazinamide (PZA) resistance in multidrug-resistant tuberculosis (MDR-TB) is common; yet, it is not clear how it affects interim and treatment outcomes. Although rarely performed, phenotypic drug susceptibility testing (pDST) is used to define PZA resistance, but genotypic DST (gDST) and minimum inhibitory concentration (MIC) could be beneficial. We aimed to assess the impact of PZA gDST and MIC on time to sputum culture conversion (SCC) and treatment outcome in patients with MDR-TB. Clinical, microbiological, and treatment data were collected in this cohort study for all patients diagnosed with MDR-TB in Sweden from 1992-2014. MIC, pDST, and whole-genome sequencing of the pncA, rpsA, and panD genes were used to define PZA resistance. A Cox regression model was used for statistical analyses. Of 157 patients with MDR-TB, 56.1% (n = 88) had PZA-resistant strains and 49.7% (n = 78) were treated with PZA. In crude and adjusted analysis (hazard ratio [HR], 0.49; 95% conficence interval [CI], .29-.82; P = .007), PZA gDST resistance was associated with a 29-day longer time to SCC. A 2-fold decrease in dilutions of PZA MIC for PZA-susceptible strains showed no association with SCC in crude or adjusted analyses (HR, 0.98; 95% CI, .73-1.31; P = .89). MIC and gDST for PZA were not associated with treatment outcome. In patients with MDR-TB, gDST PZA resistance was associated with a longer time to SCC. Rapid PZA gDST is important to identify patients who may benefit from PZA treatment.

Adjunctive vitamin D in tuberculosis treatment: meta-analysis of individual participant data.

Randomised controlled trials of adjunctive vitamin D in pulmonary tuberculosis (TB) treatment have yielded conflicting results. Individual participant data meta-analysis could identify factors explaining this variation. We meta-analysed individual participant data from randomised controlled trials of vitamin D in patients receiving antimicrobial therapy for pulmonary TB. Primary outcome was time to sputum culture conversion. Secondary outcomes were time to sputum smear conversion, mean 8-week weight and incidence of adverse events. Pre-specified subgroup analyses were done according to baseline vitamin D status, age, sex, drug susceptibility, HIV status, extent of disease and vitamin D receptor genotype. Individual participant data were obtained for 1850 participants in eight studies. Vitamin D did not influence time to sputum culture conversion overall (adjusted HR 1.06, 95% CI 0.91-1.23), but it did accelerate sputum culture conversion in participants with multidrug-resistant pulmonary TB (adjusted HR 13.44, 95% CI 2.96-60.90); no such effect was seen in those whose isolate was sensitive to rifampicin and/or isoniazid (adjusted HR 1.02, 95% CI 0.88-1.19; p-value for interaction=0.02). Vitamin D accelerated sputum smear conversion overall (adjusted HR 1.15, 95% CI 1.01-1.31), but did not influence other secondary outcomes. Vitamin D did not influence time to sputum culture conversion overall, but it accelerated sputum culture conversion in patients with multidrug-resistant pulmonary TB.

High-Dose Vitamin D3 during Tuberculosis Treatment in Mongolia. A Randomized Controlled Trial.

Existing trials of adjunctive vitamin D in the treatment of pulmonary tuberculosis (PTB) are variously limited by small sample sizes, inadequate dosing regimens, and high baseline vitamin D status among participants. Comprehensive analyses of the effects of genetic variation in the vitamin D pathway on response to vitamin D supplementation are lacking. To determine the effect of high-dose vitamin D3 on response to antimicrobial therapy for PTB and to evaluate the influence of single-nucleotide polymorphisms (SNPs) in vitamin D pathway genes on response to adjunctive vitamin D3. We conducted a clinical trial in 390 adults with PTB in Ulaanbaatar, Mongolia, who were randomized to receive four biweekly doses of 3.5 mg (140,000 IU) vitamin D3 (n = 190) or placebo (n = 200) during intensive-phase antituberculosis treatment. The intervention elevated 8-week serum 25-hydroxyvitamin D concentrations (154.5 nmol/L vs. 15.2 nmol/L in active vs. placebo arms, respectively; 95% confidence interval for difference, 125.9-154.7 nmol/L; P < 0.001) but did not influence time to sputum culture conversion overall (adjusted hazard ratio, 1.09; 95% confidence interval, 0.86-1.36; P = 0.48). Adjunctive vitamin D3 accelerated sputum culture conversion in patients with one or more minor alleles for SNPs in genes encoding the vitamin D receptor (rs4334089, rs11568820) and 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1: rs4646536) (adjusted hazard ratio ≥ 1.47; P for interaction ≤ 0.02). Vitamin D3 did not influence time to sputum culture conversion in the study population overall. Effects of the intervention were modified by SNPs in VDR and CYP27B1. Clinical trial registered with www.clinicaltrials.gov (NCT01657656).

Factors associated with sputum culture conversion in patients with pulmonary tuberculosis

ObjectiveThe aim of this study was to determine what factors are associated with sputum culture conversion after 1 month of tuberculosis (TB) treatment. Materials and methodsA total of 52 patients with new drug susceptible pulmonary TB were included in the study. Patients completed St. George respiratory questionnaire (SGRQ), they were asked about smoking, alcohol use, living conditions and education. Body mass index (BMI) measurements, laboratory tests (C reactive protein [CRP], vitamin D, albumin) were performed, and chest X-ray was done. After 1 month of treatment sputum culture was repeated. ResultsCulture conversion after 1 month of treatment was found in 38.5% cases. None of investigated social factors appeared to have an effect on conversion, but worse overall health status (as reported in SGRQ) and longer duration of tobacco smoking were detected in the “no conversion” group. Concentrations of albumin, CRP, X-ray score and the time it took Mycobacterium tuberculosis culture to grow also differed. Patients who scored 30 or more on SGRQ were more than 7 times as likely to have no conversion. However, the most important factor predicting sputum culture conversion was sputum smear grade at the beginning of treatment: patients with grade of 2+ or more had more than 20-fold higher relative risk for no conversion. Using receiver operating characteristic curve analysis, we also developed a risk score for no conversion. ConclusionsThe most important factors in predicting sputum culture conversion after 1 month of treatment were grades of acid-fast bacilli in sputum smears at time of diagnosis and scores of SGRQ.

Diabetes Reduces the Rate of Sputum Culture Conversion in Patients With Newly Diagnosed Multidrug-Resistant Tuberculosis.

Background. Diabetes is a risk factor for active tuberculosis (TB), but little is known about the relationship between diabetes and multidrug-resistant (MDR) TB. We aimed to assess risk factors for primary MDR TB, including diabetes, and determine whether diabetes reduced the rate of sputum culture conversion among patients with MDR TB. Methods. From 2011 to 2014, we conducted a cohort study at the National Center for Tuberculosis and Lung Diseases in Tbilisi, Georgia. Adult (≥35 years) patients with primary TB were eligible. Multidrug-resistant TB was defined as resistance to at least rifampicin and isoniazid. Patients with capillary glycosylated hemoglobin (HbA1c) ≥ 6.5% or previous diagnosis were defined to have diabetes. Polytomous regression was used to estimate the association of patient characteristics with drug resistance. Cox regression was used to compare rates of sputum culture conversion in patients with and without diabetes. Results. Among 318 patients with TB, 268 had drug-susceptibility test (DST) results. Among patients with DST results, 19.4% (52 of 268) had primary MDR TB and 13.4% (36 of 268) had diabetes. In multivariable analyses, diabetes (adjusted odds ratio [aOR], 2.51; 95% confidence interval [CI], 1.00-6.31) and lower socioeconomic status (aOR, 3.51; 95% CI, 1.56-8.20) were associated with primary MDR TB. Among patients with primary MDR TB, 44 (84.6%) converted sputum cultures to negative. The rate of sputum culture conversion was lower among patients with diabetes (adjusted hazard ratio [aHR], 0.34; 95% CI, .13-.87) and among smokers (aHR, 0.16; 95% CI, .04-.61). Conclusions. We found diabetes was associated with an increased risk of primary MDR TB; both diabetes and smoking were associated with a longer time to sputum culture conversion.

Particulate matter is associated with sputum culture conversion in patients with culture-positive tuberculosis.

Emerging risk factors for tuberculosis (TB) infection, such as air pollution, play a significant role at both the individual and population levels. However, the association between air pollution and TB remains unclear. The objective of this study was to examine the association between outdoor air pollution and sputum culture conversion in TB patients. In the present study, 389 subjects were recruited from a hospital in Taiwan from 2010 to 2012: 144 controls with non-TB-related pulmonary diseases with negative sputum cultures and 245 culture-positive TB subjects. We observed that a 1 μg/m3 increase in particulate matter of ≤10 μm in aerodynamic diameter (PM10) resulted in 4% higher odds of TB (odds ratio =1.04, 95% confidence interval =1.01–1.08, P<0.05). The chest X-ray grading of TB subjects was correlated to 1 year levels of PM10 (R2=0.94, P<0.05). However, there were no associations of pulmonary cavitation or treatment success rate with PM10. In subjects with TB-positive cultures, annual exposure to ≥50 μg/m3 PM10 was associated with an increase in the time required for sputum culture conversion (hazard ratio =1.28, 95% confidence interval: 1.07–1.84, P<0.05). In conclusion, chronic exposure to ≥50 μg/m3 PM10 may prolong the sputum culture conversion of TB patients with sputum-positive cultures.

Adjunctive vitamin D for treatment of active tuberculosis in India: a randomised, double-blind, placebo-controlled trial

Vitamin D has immunomodulatory effects that might aid clearance of mycobacterial infection. We aimed to assess whether vitamin D supplementation would reduce time to sputum culture conversion in patients with active tuberculosis. We did this randomised, double-blind, placebo-controlled, superiority trial at 13 sites in India. Treatment-naive patients who were sputum-smear positive, HIV negative, and had pulmonary tuberculosis were randomly assigned (1:1), with centrally labelled, serially numbered bottles, to receive standard active tuberculosis treatment with either supplemental high-dose oral vitamin D3 (four doses of 2·5 mg at weeks 0, 2, 4, and 6) or placebo. Neither the patients nor the clinical and laboratory investigators and personnel were aware of treatment assignment. The primary efficacy outcome was time to sputum culture conversion. Analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00366470. Between Jan 20, 2010, and Aug 23, 2011, we randomly assigned 247 participants to the vitamin D group (n=121) or the placebo group (n=126), of whom 211 participants (n=101 and n=110, respectively) were included in the primary efficacy analysis. Median time to culture conversion in the vitamin D group was 43·0 days (95% CI 33·3-52·8) versus 42·0 days (33·9-50·1) in the placebo group (log-rank p=0·95). Three (2%) patients died in the vitamin D group and one (1%) patient died in the placebo group; no death was considered attributable to the study intervention. No patients had hypercalcaemia. Our findings show that vitamin D supplementation did not reduce time to sputum culture conversion. Further studies should investigate the role of vitamin D in prevention or reactivation of tuberculosis infection. Dalhousie University and Infectious Diseases Training and Research Centre.

Profile of delamanid for the treatment of multidrug-resistant tuberculosis.

New approaches to the treatment of multidrug-resistant and extensively drug-resistant tuberculosis (TB) are badly needed. Not only is the success rate of current treatment regimens suboptimal but existing regimens require multiple drugs and lengthy courses and may lead to significant toxicities. The treatment landscape is beginning to shift, however, with the recent approvals of the new TB drugs bedaquiline and delamanid. Delamanid, a dihydro-imidazooxazole, has been shown to have excellent activity against Mycobacterium tuberculosis in both in vitro and in murine TB models. It has also recently been reported to improve rates of sputum culture conversion in patients with multidrug-resistant TB when added to an optimized background regimen. Although generally well tolerated, delamanid has been associated with QT prolongation, which may be of particular clinical concern when paired with other TB drugs that may also have this effect, most notably the fluoroquinolones. Ongoing studies will help to clarify delamanid’s role in the treatment of drug-resistant TB.

Multidrug-Resistant Tuberculosis and Culture Conversion with Bedaquiline

BackgroundBedaquiline (Sirturo, TMC207), a diarylquinoline that inhibits mycobacterial ATP synthase, has been associated with accelerated sputum-culture conversion in patients with multidrug-resistant tuberculosis, when added to a preferred background regimen for 8 weeks.MethodsIn this phase 2b trial, we randomly assigned 160 patients with newly diagnosed, smear-positive, multidrug-resistant tuberculosis to receive either 400 mg of bedaquiline once daily for 2 weeks, followed by 200 mg three times a week for 22 weeks, or placebo, both in combination with a preferred background regimen. The primary efficacy end point was the time to sputum-culture conversion in liquid broth. Patients were followed for 120 weeks from baseline.ResultsBedaquiline reduced the median time to culture conversion, as compared with placebo, from 125 days to 83 days (hazard ratio in the bedaquiline group, 2.44; 95% confidence interval, 1.57 to 3.80; P<0.001 by Cox regression analysis) and increased the rate of culture conversion at 24 weeks (79% vs. 58%, P=0.008) and at 120 weeks (62% vs. 44%, P=0.04). On the basis of World Health Organization outcome definitions for multidrug-resistant tuberculosis, cure rates at 120 weeks were 58% in the bedaquiline group and 32% in the placebo group (P=0.003). The overall incidence of adverse events was similar in the two groups. There were 10 deaths in the bedaquiline group and 2 in the placebo group, with no causal pattern evident.ConclusionsThe addition of bedaquiline to a preferred background regimen for 24 weeks resulted in faster culture conversion and significantly more culture conversions at 120 weeks, as compared with placebo. There were more deaths in the bedaquiline group than in the placebo group. (Funded by Janssen Pharmaceuticals; TMC207-C208 ClinicalTrials.gov number, NCT00449644.)

Diabetes mellitus, smoking status, and rate of sputum culture conversion in patients with multidrug-resistant tuberculosis: a cohort study from the country of Georgia.

IntroductionDiabetes mellitus (DM) is a risk factor for active tuberculosis (TB) but little is known about the effect of DM on culture conversion among patients with multidrug-resistant (MDR)-TB. The primary aim was to estimate the association between DM and rate of TB sputum culture conversion. A secondary objective was to estimate the association between DM and the risk of poor treatment outcomes among patients with MDR-TB.Materials and MethodsA cohort of all adult patients starting MDR-TB treatment in the country of Georgia between 2009–2011 was followed during second-line TB therapy. Cox proportional models were used to estimate the adjusted hazard rate of sputum culture conversion. Log-binomial regression models were used to estimate the cumulative risk of poor TB treatment outcome.ResultsAmong 1,366 patients with sputum culture conversion information, 966 (70.7%) had culture conversion and the median time to conversion was 68 days (interquartile range 50–120). The rate of conversion was similar among patients with MDR-TB and DM (adjusted hazard ratio [aHR] 0.95, 95%CI 0.71–1.28) compared to patients with MDR-TB only. The rate of culture conversion was significantly less in patients that currently smoked (aHR 0.82, 95%CI 0.71–0.95), had low body mass index (aHR 0.71, 95%CI 0.59–0.84), second-line resistance (aHR 0.56, 95%CI 0.43–0.73), lung cavities (aHR 0.70, 95%CI 0.59–0.83) and with disseminated TB (aHR 0.75, 95%CI 0.62–0.90). The cumulative risk of poor treatment outcome was also similar among TB patients with and without DM (adjusted risk ratio [aRR] 1.03, 95%CI 0.93–1.14).ConclusionsIn adjusted analyses, DM did not impact culture conversion rates in a clinically meaningful way but smoking did.

HIV infection and sputum-culture conversion in patients diagnosed with Mycobacterium tuberculosis: a population-based study.

To estimate the effect of human immunodeficiency virus infection on treatment outcome of anti-tuberculosis therapy at the population level. A retrospective cohort study based on data collected through the expanded program on tuberculosis surveillance on all reported and verified cases of tuberculosis in the State of North Carolina from 1993 to 1998. Eligible patients were sputum-positive at baseline, with known and documented HIV-serology status. We analyzed 1030 cases consisting of 210 HIV-positive and 820 HIV-negative tuberculosis patients. Patients were followed up for 12 months to document sputum conversion. Among HIV-infected individuals, 60% (126) converted compared to 75% (615) of HIV-uninfected persons. Using the Cox Proportional Hazard method to estimate the likelihood of conversion, we found the difference in conversion rates to be highly significant (crude hazard ratio = 0.54, CI = 0.45-0.66). The inverse relationship between HIV-seropositivity and sputum conversion still persisted and remained practically unchanged after adding potential confounding factors into the model (adjusted hazard ratio = 0.56, 95% CI = 0.46-0.69). Response to anti-tuberculosis therapy was significantly less favorable in HIV-infected than in HIV-uninfected tuberculosis patients. The importance of longer and closer monitoring of tuberculosis treatment in HIV-positive patients is highlighted.